Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.564
Filtrar
1.
Ann Agric Environ Med ; 27(3): 394-400, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955221

RESUMO

INTRODUCTION: Overweight and obesity, as well as a gonadal function, are pivotal factors influencing bone tissue metabolism. MATERIAL AND METHODS: The aim of the study was to determine the effect of dietary induced obesity (DIO) on bone tissue metabolism in sham-operated (SHO) or ovariectomized (OVX) adult female Wistar rats. Additionally, the influence of DIO in SHO or OVX on the concentration of sclerostin in the blood serum was analyzed. After SHO or OVX, the rats were placed in groups (n=8) and either received a standard diet (11.5 MJ/kg) (SHO-CON; OVX-CON) or a high-energy diet (17.6 MJ/kg) (SHO-FAT; OVX-FAT). The experiment lasted for 90 days and allowed for the establishment of osteopenia in OVX females and obesity in the rats that had received the high-energy diet. RESULTS: The results of the study demonstrate that obesity or/and ovariectomy increases the resorption of femora and tibiae, hence decreasing the densitometric and mechanical parameters affecting the bone structure in adult females rats. The strongest osteodegenerative effect was seen in the OVX-FAT females. Interestingly, the degree of bone tissue degradation caused exclusively by ovariectomy was similar to that found in the obese sham-operated rats. CONCLUSIONS: Bone losses invoked by DIO seem to be independent from the Wnt/ß-catenin pathway inhibition induced by sclerostin. While further study is necessary, the obtained results suggest that the usage of sclerostin anti-body in the treatment of osteoporosis can be ineffective, and in obese patients the undertaking of such therapy should be reassessed.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Osso e Ossos/metabolismo , Dieta/efeitos adversos , Obesidade/complicações , Ovariectomia/efeitos adversos , Via de Sinalização Wnt , Animais , Reabsorção Óssea , Feminino , Marcadores Genéticos , Humanos , Obesidade/etiologia , Ratos , Ratos Wistar
2.
Life Sci ; 256: 117975, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32565251

RESUMO

Our goal is to understand how loss of circulating estrogens and estrogen replacement affect brain physiology and function, particularly in brain regions involved in cognitive processes. We recently conducted a large metabolomics study characterizing the effects of rodent models of menopause and treatment with estrogen receptor (ER) agonists on neurochemical targets in hippocampus, frontal cortex, and striatum. Here we characterize effects on levels of several key enzymes involved in glucose utilization and energy production, specifically phosphofructokinase, glyceraldehyde 3-phosphate dehydrogenase, and pyruvate dehydrogenase. We also evaluated effects on levels of ß-actin and α-tubulin, choline acetyltransferase (ChAT) activity, and levels of ATP citrate lyase. All experiments were conducted in young adult rats. Experiment 1 compared the effects of ovariectomy (OVX), a model of surgical menopause, and 4-vinylcyclohexene diepoxide (VCD)-treatments, a model of transitional menopause, with tissues collected at proestrus and at diestrus. Experiment 2 used a separate cohort of rats to evaluate the same targets in OVX and VCD-treated rats treated with estradiol or with selective ER agonists. Differences in the expression of metabolic enzymes between cycling animals and models of surgical and transitional menopause were detected. These differences were model-, region- and time- dependent, and were modulated by selective ER agonists. Collectively, the findings demonstrate that loss of ovarian function and ER agonist treatments have differing effects in OVX vs. VCD-treated rats. Differences may help to explain differences in the effects of estrogen treatments on brain function and cognition in women who have experienced surgical vs. transitional menopause.


Assuntos
Acetilcoenzima A/metabolismo , Encéfalo/metabolismo , Colina O-Acetiltransferase/metabolismo , Estrogênios/farmacologia , Menopausa/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Cicloexenos/toxicidade , Estradiol/sangue , Feminino , Menopausa/efeitos dos fármacos , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Compostos de Vinila/toxicidade
3.
Am J Chin Med ; 48(2): 463-485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32138532

RESUMO

Oxidative stress (OS) is the common mechanism for age-related diseases. The co-occurrence of osteoporosis (OP) and cardiovascular disease (CVD) in postmenopausal women makes it warranted to find a holistic approach for treatment of multiple diseases or conditions. The rhizome of Ligusticum chuanxiong Hort. (CX), which has high anti-oxidant properties and is widely used for CVD treatment in China, might be the potential candidate. In the present study, CX ethanol extract (CXE) was applied to H2O2 induced MG63 cells to study its effects and mechanisms on osteoblastogenesis against OS. CXE was then administered to six-month-old Sprague Dawley sham or ovariectomized (OVX) rats fed either a low saturated fat-sucrose (LFS) or a high fat-sucrose (HFS) diet for 12 weeks, to confirm its anti-osteoporotic effects. The results demonstrated that CXE directly improved proliferation and differentiation in vitro in an H2O2-induced osteoblast cell model by attenuating cellular reactive oxygen species levels and inhibiting osteoblast apoptosis via PI3K/Akt signaling pathway. CXE significantly improved bone properties as revealed by the increase in trabecular bone mineral density and decrease in trabecular separation at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats but not in LFS-fed OVX rats. CXE ameliorated dyslipidemia, greatly reduced lipid deposition and malondialdehyde levels, improved activities of superoxide dismutase, catalase and glutathione peroxidase in the livers of HFS-fed OVX rats. In conclusion, CXE could favor osteoblastogenesis against OS. The ability of CXE to reduce bone loss in HFS-fed OVX rats was associated with its abilities to correct dyslipidemia, and reduce lipid deposition and OS levels.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/complicações , Osteoporose/etiologia , Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Animais , Células Cultivadas , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Osteoblastos/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Biol Pharm Bull ; 43(3): 546-549, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115513

RESUMO

Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.


Assuntos
Estrogênios/deficiência , Alho , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Ovariectomia/efeitos adversos , Extratos Vegetais/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Memória/efeitos dos fármacos , Ratos
5.
Artigo em Inglês | MEDLINE | ID: mdl-32192936

RESUMO

Primary surgical prevention in the form of risk-reducing salpingo-oophorectomy (RRSO) is the most effective option and the gold standard for ovarian cancer (OC) risk-reduction, particularly given the absence of an effective national OC screening programme. However, premenopausal RRSO leads to premature surgical menopause with detrimental long-term health sequelae particularly in women who do not/are unable to take hormone replacement therapy (HRT). HRT uptake in women undergoing pre-menopausal oophorectomy appears low and is dependent on informed counselling, the safety of HRT and efficacy in mitigating the health sequelae of premature menopause. Acceptance of a central role for the fallopian tube in OC etiopathogenesis, coupled with the detrimental consequences of premature menopause, has led to the attractive proposal of early-salpingectomy with delayed oophorectomy as an alternative OC surgical prevention strategy in premenopausal women who have completed childbearing but decline or wish to delay RRSO. The successful implementation of risk reducing surgery for OC prevention depends on the acceptability of surgery to both, recipients (e.g. BRCA1/BRCA2 carriers) and intervention deliverers (healthcare professionals/researchers). Acceptability is also informed by an understanding of health outcomes following risk reducing surgery and the safety of HRT. It is therefore vital to understand the effects of surgery on important health outcomes such as cardiovascular health, neurological function and bone health. We present a comprehensive review of acceptability, the selected health outcomes mentioned above and HRT safety following risk reducing surgery.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Densidade Óssea/fisiologia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Ovariectomia/métodos , Salpingectomia/métodos , Salpingo-Ooforectomia/métodos , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Feminino , Predisposição Genética para Doença , Heterozigoto , Terapia de Reposição Hormonal , Humanos , Mutação , Neoplasias Ovarianas/genética , Ovariectomia/efeitos adversos , Salpingectomia/efeitos adversos , Salpingo-Ooforectomia/efeitos adversos
6.
Toxicol Appl Pharmacol ; 393: 114928, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32092384

RESUMO

The female gender is protected against immunological complications of endotoxemia. Here we investigated whether gonadal hormone depletion by ovariectomy (OVX) uncovers inflammatory and cardiovascular effects of endotoxemia and whether these effects are reversed by hormone replacement therapies. Changes in inflammatory cytokines, blood pressure (BP), left ventricular (LV) function, and cardiac autonomic activity caused by lipopolysaccharide (LPS) in conscious female rats with different hormonal states were determined. In contrast to no effects in sham-operated females, treatment of OVX rats with LPS (i) decreased BP, (ii) increased spectral low-frequency/high-frequency ratio of HRV, denoting enhanced cardiac sympathetic dominance, (iii) attenuated reflex tachycardic responses to sodium nitroprusside, and (iv) increased systolic contractility (dP/dtmax). The developed hypotension was (i) fully eliminated in estrogen (E2)-pretreated OVX rats, (ii) partially counteracted after selective activation of estrogen receptor-α (PPT) or ß (DPN). All estrogenic compounds abrogated LPS enhancement of cardiac sympathetic drive. However, PPT was more successful than E2 or DPN in compromising LPS depression in baroreflex activity and elevation in dP/dtmax. Molecular studies showed that PPT was most effective in attenuating the upregulated myocardial expressions of NF-κB and iNOS in endotoxic OVX rats. Myocardial expression of the defensive HSP70 was comparably increased by all estrogenic products. Except for improved cardiac spectral activity, none of these functional or molecular entities was affected by medroxyprogesterone acetate (MPA). Overall, our data suggest diverse therapeutic advantages for gonadal hormones in the worsened endotoxic complications in rats with surgical menopause, with probably more favorable role for ERα agonism within this context.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Endotoxemia/complicações , Endotoxemia/tratamento farmacológico , Terapia de Reposição de Estrogênios/métodos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Ovariectomia/efeitos adversos , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea , Citocinas , Endotoxemia/induzido quimicamente , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/agonistas , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Lipopolissacarídeos , Acetato de Medroxiprogesterona/uso terapêutico , Ratos , Ratos Wistar , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos
8.
Int. j. morphol ; 38(1): 129-134, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056410

RESUMO

Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.


Las complicaciones de la menopausia, como las enfermedades cardiovasculares y óseas, representan un importante problema de salud pública. Intentamos determinar si una dieta alta en grasas (HFD) puede aumentar la resorción ósea inducida por ovariectomía en un modelo de menopausia en ratas, a través de la regulación positiva de los biomarcadores inflamatorios y la dislipidemia. Las ratas fueron ovariectomizadas y alimentadas con una comida estándar de laboratorio (grupo modelo) o fueron ovariectomizadas y alimentadas con un HFD durante 15 semanas antes de ser sacrificadas. La ovariectomía aumentó significativamente (p <0,05) el peso corporal, dislipidemia, resistencia a la insulina, citocinas proinflamatorias, factor de necrosis tumoral a (TNF-α) e interleucina-6 (IL-6), y el biomarcador de resorción ósea, factor nuclear-kB (NF-kB), que se aumentaron alimentando animales con un HFD. Esto se confirmó a través del estudio inmunohistoquímico, donde la ovariectomía indujo la expresión de la proteína p65 / NF-kB en secciones de hueso de tibia del grupo modelo, que fueron aumentadas por HFD. HFD aumenta la resorción ósea inducida por ovariectomía a través del aumento de biomarcadores inflamatorios y NF-kB en ratas.


Assuntos
Animais , Feminino , Ratos , Reabsorção Óssea/patologia , Dieta Hiperlipídica/efeitos adversos , Triglicerídeos/análise , Reabsorção Óssea/etiologia , Resistência à Insulina , Menopausa , Ovariectomia/efeitos adversos , Ratos Wistar , Modelos Animais de Doenças , Dislipidemias/complicações
9.
PLoS One ; 15(2): e0228559, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045430

RESUMO

The risk of metabolic abnormalities in menopausal women increases significantly due to the decline in estrogen level. Nuclear factor E2-related factor 2 (NRF2) is an important oxidative stress sensor that plays regulatory role in energy metabolism. Therefore, an ovariectomized menopausal model in Nrf2-knockout (KO) mice was applied to evaluate the effect of Nrf2 deficiency on metabolism in menopausal females. The mice were divided into four groups according to their genotypes and treatments. Blood samples and bodyweights were obtained preoperatively and in the first to ninth postoperative weeks after overnight fasting. Serum levels of triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and glucose (GLU) were measured at postoperative weeks 0, 1, 3, 5, 7, and 9. Neurotransmitter dopamine (DA) and serotonin (5-HT) was analyzed in brain tissues after sacrifice at postoperative week 9. The results demonstrated that, compared with the corresponding wild-type (WT) mice, KO ovariectomized mice had a greater bodyweight gain (P<0.01). Serum analysis showed that the serum GLU, T-CHO, and TG were significantly lower (P<0.05) but LDL was significantly higher (P<0.05) in the KO control mice than that in WT control mice. However, different from the WT counterparts, an increase in blood GLU level (P<0.05), unchanged T-CHO, TG, and HDL levels, and a significant reduction in LDL (P<0.01) was found in the KO ovariectomized mice. In addition, the level of 5-HT was significantly reduced (P<0.05) in the KO mice after ovariectomy. In conclusion, the combination of Nrf2 deletion and a decline in estrogen level induced a significant increase in bodyweight, which may be associated with their altered glucose and LDL metabolism and decreased 5-HT levels. From a clinical perspective, women with antioxidant defense deficiency may have an increased risk of metabolic abnormalities after menopause.


Assuntos
Estrogênios/deficiência , Fator 2 Relacionado a NF-E2/deficiência , Obesidade/genética , Animais , Glicemia/análise , Encéfalo/metabolismo , Dopamina/metabolismo , Feminino , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Obesidade/etiologia , Ovariectomia/efeitos adversos , Serotonina/metabolismo
10.
EBioMedicine ; 52: 102626, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31981979

RESUMO

BACKGROUND: Forkhead box protein f1 (Foxf1) is associated with cell differentiation, and may be a key player in bone homoeostasis. However, the effect of Foxf1 on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) and ovariectomy-induced bone loss, as well as its clinical implications, is unknown. METHODS: By quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, we assayed Foxf1 expression in bone tissue, BMSCs, and bone marrow-derived macrophages (BMMs), derived from ovariectomised (OVX) mice, and during osteogenic differentiation and osteoclast differentiation. Using a loss-of-function approach (small interfering RNA [siRNA]-mediated knockdown) in vitro, we examined whether Foxf1 regulates osteoblast differentiation of BMSCs via the Wnt/ß-catenin signalling pathway. Furthermore, we assessed the anabolic effect of Foxf1 knockdown (siFoxf1) in OVX mice in vivo. We also assayed the expression of Foxf1 in bone tissue derived from postmenopausal osteoporosis (PMOP) patients and its link with bone mineral density (BMD). Finally, we examined the effect of Foxf1 knockdown on the osteoblastic differentiation of human BMSCs. FINDINGS: Foxf1 expression was significantly increased in bone extract and BMSCs from OVX mice and gradually decreased during osteoblastic differentiation of BMSCs but did not differ significantly in OVX mouse-derived BMMs or during osteoclast differentiation. In vitro, Foxf1 knockdown markedly increased the expression of osteoblast specific genes, alkaline phosphatase (ALP) activity, and mineralisation. Moreover, siFoxf1 activated the Wnt/ß-catenin signalling pathway. The siFoxf1-induced increase in osteogenic differentiation was partly rescued by inhibitor of Wnt signalling (DKK1). In OVX mice, Foxf1 siRNA significantly reduced bone loss by enhancing bone formation. Foxf1 expression levels negatively correlated with reduced bone mass and bone formation in bone tissue from PMOP patients. Finally, Foxf1 knockdown significantly promoted osteogenesis by human BMSCs. INTERPRETATION: Our findings indicate that Foxf1 knockdown promotes BMSC osteogenesis and prevents OVX-induced bone loss. Therefore, Foxf1 has potential as a biomarker of osteogenesis and may be a therapeutic target for PMOP.


Assuntos
Fatores de Transcrição Forkhead/deficiência , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Via de Sinalização Wnt , Adulto , Animais , Biomarcadores , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Microtomografia por Raio-X , Adulto Jovem
11.
Mar Drugs ; 18(2)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991543

RESUMO

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in ovariectomized rats. Sprague-Dawley female rats (9 weeks old) were acclimatized for a week and randomly divided into three groups (n = 15 each group) as follows: group I (sham-operated rats, SHAM), group II (ovariectomized rats, OVX), group III (ovariectomized rats treated with ECH, OVX + ECH). Rats from the OVX + ECH group were intraperitoneally injected with ECH at 10 mg/kg thrice a week after surgery for 6 weeks. And rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in OVX group compared with the SHAM group. ECH treatment had no effect on the levels of estradiol and expression of estrogen receptor ß (ERß). The evaluation of ECM components showed no significant changes in elastin and hyaluronic acid levels between the different groups. Collagen I and III levels were lower in OVX group than in SHAM group but increased in OVX + ECH group. The mRNA levels of matrix metalloproteinase (MMP)-1, -2, -8, and -9 were significantly higher in the OVX group than in the SHAM group, but decreased in the OVX + ECH group. Thus, changes were observed in ECM-related genes in the OVX group upon estradiol deficiency that were ameliorated by ECH administration. Thus, the vocal fold is an estradiol-sensitive target organ and ECH may have protective effects on the ECM of vocal folds in ovariectomized rats.


Assuntos
Estradiol/deficiência , Matriz Extracelular/efeitos dos fármacos , Naftoquinonas/administração & dosagem , Prega Vocal/efeitos dos fármacos , Vocalização Animal/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Feminino , Humanos , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Prega Vocal/citologia , Prega Vocal/fisiologia , Vocalização Animal/fisiologia
12.
Life Sci ; 244: 117336, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972206

RESUMO

AIMS: Postmenopausal osteoporosis and other osteolytic bone diseases are often caused by the elevation in osteoclastogenesis and/or increased osteoclastic bone resorption, leading to excessive bone loss. Hederagenin (Hed) is a pentacyclic triterpenoid saponin extracted from various natural medicinal plants and exhibits numerous biological activities and may offer benefits against bone-related conditions. We evaluated the effects of Hed on osteoclast formation and bone resorption in vitro and the in vivo therapeutic benefits in the mouse model of ovariectomy (OVX)-induced bone loss. MAIN METHODS: In vitro, osteoclast formation were determined by TRAcp staining; bone resorption were examined using Hydroxyapatite resorption assay and Podosomal actin belt formation assay; Related molecular mechanisms were determined by western blot assay. Construction of OVX mice by bilateral oophorectomy to simulate bone loss in vivo. KEY FINDINGS: In vitro cellular assays showed that Hed inhibited RANKL-induced osteoclast formation and osteoclast bone (hydroxyapatite) resorption as well as marker gene expression from BMM culture. Mechanistically, Hed attenuated RANKL-induced intracellular reactive oxygen species (ROS) production, and MAPK signaling pathway (ERK and p38) activation which curbed the downstream induction of c-Fos and NFATc1. Consistent with the in vitro findings, Hed administration effectively protected OVX mice from bone loss by reducing osteoclast number and activity on bone surface. SIGNIFICANCE: Our data provided promising evidence for the potential use of Hederagenin in the treatment of osteoclast-mediated osteolytic bone diseases such as postmenopausal osteoporosis.


Assuntos
Reabsorção Óssea/prevenção & controle , Ácido Oleanólico/análogos & derivados , Osteogênese/efeitos dos fármacos , Ovariectomia/efeitos adversos , Substâncias Protetoras/farmacologia , Ligante RANK/metabolismo , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Feminino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Ácido Oleanólico/farmacologia , Ligante RANK/genética , Transdução de Sinais
13.
Redox Biol ; 28: 101309, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31487581

RESUMO

The dysregulation of ROS production and osteoclastogenesis is involved in the progress of osteoporosis. To identify novel and effective targets to treat this disease, it is important to explore the underlying mechanisms. In our study, we firstly tested the effect of the Nrf2 activator RTA-408, a novel synthetic triterpenoid under clinical investigation for many diseases, on osteoclastogenesis. We found that it could inhibit osteoclast differentiation and bone resorption in a time- and dose-dependent manner. Further, RTA-408 enhanced the expression and activity of Nrf2 and significantly suppressed RANKL-induced reactive oxygen species (ROS) production. Nrf2 regulates the STING expression and STING induces the production of IFN-ß. Here, we found that RTA-408 could suppress STING expression, but that it does not affect Ifnb1 expression. RANKL-induced degradation of IκBα and the nuclear translocation of P65 was suppressed by RTA-408. Although this compound was not found to influence STING-IFN-ß signaling, it suppressed the RANKL-induced K63-ubiquitination of STING via inhibiting the interaction between STING and the E3 ubiquitin ligase TRAF6. Further, adenovirus-mediated STING overexpression rescued the suppressive effect of RTA-408 on NF-κB signaling and osteoclastogenesis. In vivo experiments showed that this compound could effectively attenuate ovariectomy (OVX)-induced bone loss in C57BL/6 mice by inhibiting osteoclastogenesis. Collectively, we show that RTA-408 inhibits NF-κB signaling by suppressing the recruitment of TRAF6 to STING, in addition to attenuating osteoclastogenesis and OVX-induced bone loss in vivo, suggesting that it could be a promising candidate for treating osteoporosis in the future.


Assuntos
Macrófagos/citologia , Células-Tronco Mesenquimais/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Oleanólico/administração & dosagem , Osteoporose/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Ácido Oleanólico/farmacologia , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Ligante RANK/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
14.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875222

RESUMO

Ovariectomy (spaying) using the trans-vaginal dropped ovary technique (DOT) is performed to prevent pregnancy in cull female beef cattle that are not retained for breeding stock in areas practicing extensive grazing management. There are no reports describing analgesia for this surgical procedure. The objective of this study was to measure behavioral and physiological responses to determine whether an analgesic protocol of BXK [butorphanol (0.01 mg/kg), xylazine (0.02 mg/kg), and ketamine (0.04 mg/kg)] injected intramuscularly (i.m.) before spaying could mitigate procedural and immediate postsurgical pain, and whether oral meloxicam (1 mg/kg) administered at the time of spaying could mitigate postsurgical inflammatory pain. Forty-four red Angus and Angus crossbred yearling heifers (322 ± 27.0 kg BW) were randomly allocated to 1 of 3 groups: PALP (control; palpated but not spayed; n = 14), SPAY (spayed with no analgesia; n = 15), and BXKM (spayed with analgesia; n = 15). Behavioral measurements included visual analog scale (VAS) score, flight speed (FS), stride length (SL), and gait score (GS), as well as activity (lying, standing) and feeding behavior. Physiological measurements included salivary cortisol (SC), haptoglobin (Hp), serum amyloid A (SAA), substance P (SP), complete blood count (CBC), and rectal temperature (RT). Saliva and blood samples were collected, and RT, FS, SL, and GS were measured on day -1, day 0 (time of palpation/spaying), and hours 1, 2, 4, and days 1, 2, 4, and 7 after palpation/spaying. The BXKM heifers had lower SC concentrations than SPAY heifers at 1 h (P = 0.01) and 2 h (P = 0.004). Heifers treated with BXKM had Hp concentrations lower than SPAY heifers at 2 d (P = 0.01), 4 d (P < 0.001), and 7 d (P = 0.008), and lower Hp concentrations than PALP heifers at 4 d (P < 0.001). Concentrations of SAA were greater (P = 0.04) in BXKM heifers than in PALP heifers at 1 h and lower in PALP heifers than in BXKM heifers (P = 0.02) and SPAY heifers (P = 0.05) at 1 d. Heifers in the BXKM group had higher RT than PALP and SPAY heifers at 1 h (P < 0.001) and 2 h (P = 0.004). Results suggest that DOT ovariectomy is acutely stressful and painful and administration of BXK before spaying and meloxicam at the time of spaying mitigated the procedural and postsurgical stress, pain, and inflammation.


Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Bovinos/fisiologia , Inflamação/veterinária , Meloxicam/administração & dosagem , Ovariectomia/veterinária , Bem-Estar do Animal , Animais , Biomarcadores/análise , Cruzamento , Bovinos/cirurgia , Feminino , Inflamação/prevenção & controle , Inflamação/terapia , Ovariectomia/efeitos adversos , Ovário/cirurgia , Dor/prevenção & controle , Dor/veterinária
15.
PLoS One ; 14(12): e0223709, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805064

RESUMO

Spaying of female dogs is a widespread practice, performed primarily for population control. While the consequences of early spaying for health are still being debated, the consequences for behaviour are believed to be negligible. The current study focused on the reported behaviour of 8981 female dogs spayed before 520 weeks (ten years) of life for reasons other than behavioural management, and calculated their percentage lifetime exposure to gonadal hormones (PLGH) as a proportion of their age at the time of being reported to the online Canine Behavioral Assessment and Research Questionnaire (C-BARQ). We found that 23 behaviours differed between entire and spayed dogs, of which 12 were associated with PLGH and 5 with age-at-spay (AAS). Two behaviours, chewing and howling, were significantly more likely in dogs with longer PLGH. In contrast, longer PLGH was associated with significantly reduced reporting of 10 (mostly unwelcome) behaviours. Of these, one related to fearfulness and three to aggression. The current data suggest that dogs' tendency to show numerous behaviours can be influenced by the timing of spaying. They indicate how female dog behaviour matures when gonadal hormones are allowed to have their effect. The differences reported here between undesirable behaviours of spayed and entire dogs were in the range of 5.33% and 7.22%, suggesting that, for some dogs, partial or complete denial of maturation may reduce howling and chewing and improve retrieval and recall, but have other undesirable consequences. Veterinarians may take these data into account to discuss the risks and benefits of spaying with clients, and the timing of the procedure.


Assuntos
Doenças do Cão/etiologia , Cães/cirurgia , Hormônios Gonadais/farmacologia , Transtornos Mentais/veterinária , Ovariectomia/veterinária , Fatores Etários , Animais , Doenças do Cão/psicologia , Cães/psicologia , Feminino , Transtornos Mentais/etiologia , Ovariectomia/efeitos adversos , Ovariectomia/psicologia , Medição de Risco , Inquéritos e Questionários
16.
Oxid Med Cell Longev ; 2019: 9714302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827717

RESUMO

Morinda citrifolia (Rubiaceae) or Noni was previously reported to have leaf with broad therapeutic property whereas the fruit was rarely described as medicinal. Ironically, extensive research and review has been done on the fruit and little was known about the therapeutic activity of the leaf as a medicinal food. The aim of this study was to investigate the therapeutic effects of Morinda citrifolia (MC) ethanolic leaf extract on the hepatic structure and function in postmenopausal rats fed with thermoxidized palm oil (TPO) diet. Thirty eight female Sprague Dawley rats were divided into five groups: sham (Sham), ovariectomized (OVX), ovariectomized and treated with simvastatin 10 mg/kg (OVX+ST), ovariectomized and supplemented with low dose MC 500 mg/kg (OVX+MCLD), and ovariectomized and supplemented with high dose MC 1000 mg/kg (OVX+MCHD). All the ovariectomized groups were fed with TPO diet whereas the Sham group was fed with normal diet. Consumption of TPO diet in postmenopausal rats resulted in obesity, significantly elevated (P < 0.05) liver oxidative stress marker; malondialdehyde (MDA), diffuse microvesicular steatosis, and defective mitochondria. Treatment with MC leaf extract prevented hepatic steatosis by significantly increasing (P < 0.05) the liver antioxidant enzyme SOD and GPx, significantly increasing (P < 0.05) ALP, decreasing liver lipids infiltration, preventing mitochondrial damage, and overall maintaining the normal liver histology and ultrastructure. In conclusion, we provided detailed histological and ultrastructural evidence showing hepatoprotective effects of MC leaf extract through its antioxidant mechanism.


Assuntos
Hepatopatias/prevenção & controle , Morinda/química , Ovariectomia/efeitos adversos , Óleo de Palmeira/toxicidade , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Feminino , Temperatura Alta , Lipídeos/análise , Hepatopatias/etiologia , Hepatopatias/patologia , Oxirredução , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley
17.
Molecules ; 24(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847138

RESUMO

Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17ß-estradiol attenuated ovariectomy-induced depression-like behavior, as indicated by a decrease in immobility times in the tail suspension test (TST) and the forced swimming test (FST), an increase in the uterine weight and volume, a decrease in serum corticosterone levels, and dose-dependently normalized the downregulated transcription of the brain-derived neurotrophic factor (BDNF) and estrogen receptor (Erß and Erα) mRNAs. Like 17ß-estradiol, puerarin also inhibited ovariectomy-induced suppression of neurogenesis in the dentate gyrus of the hippocampus (increased the number of doublecortin (DCX)-immunosuppressive cells). These results suggest that puerarin exerts antidepressant-like effects in OVX animals, possibly by attenuating the OVX-induced hyperactivation of the HPA axis and/or normalizing the downregulated transcription of BDNF and ER mRNA in the brain.


Assuntos
Depressão/tratamento farmacológico , Estradiol/administração & dosagem , Isoflavonas/administração & dosagem , Ovariectomia/efeitos adversos , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Corticosterona/sangue , Depressão/etiologia , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Isoflavonas/farmacologia , Camundongos , Camundongos Endogâmicos ICR
18.
BMC Musculoskelet Disord ; 20(1): 560, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31759393

RESUMO

BACKGROUND: This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model. METHODS: Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups. RESULTS: Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters. CONCLUSION: BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Ovariectomia/efeitos adversos , Ocitocina/uso terapêutico , Microtomografia por Raio-X/métodos , Animais , Densidade Óssea/fisiologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Feminino , Imageamento Tridimensional/métodos , Ovariectomia/tendências , Ocitocina/farmacologia , Coelhos , Distribuição Aleatória
19.
BMC Musculoskelet Disord ; 20(1): 556, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747888

RESUMO

BACKGROUND: Previous studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats. METHODS: The PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, and Chinese Sinomed databases were searched systematically from their initiation date to October 5, 2018. Two researchers independently screened the literatures, which used the bone mineral density (BMD), total bone volume by total tissue volume (BV/TV) (%), and trabecular thickness/spacing (Tb/Sp) as the outcome measures. RESULTS: Five eligible studies were selected. In the BMSC treatment groups, the BMD values and normalized BV/TV values remarkably increased. In addition, in the BMSCs plus other treatment groups, the BMD and Tb/Sp values significantly increased. CONCLUSION: This study showed that BMSCs could accelerate callus maturity, ossification and restore mechanical properties of bones in osteoporotic fractures.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/terapia , Ovariectomia/tendências , Animais , Feminino , Humanos , Osteoporose Pós-Menopausa/etiologia , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley
20.
Molecules ; 24(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623098

RESUMO

Oleoyl serine (OS), an endogenous fatty acyl amide (FAA) found in bone, has been shown to have an anti-osteoporotic effect. OS, being an amide, can be hydrolyzed in the body by amidases. Hindering its amide bond by introducing adjacent substituents has been demonstrated as a successful method for prolonging its skeletal activity. Here, we tested the therapeutic efficacy of two methylated OS derivatives, oleoyl α-methyl serine (HU-671) and 2-methyl-oleoyl serine (HU-681), in an ovariectomized mouse model for osteoporosis by utilizing combined micro-computed tomography, histomorphometry, and cell culture analyses. Our findings indicate that daily treatment for 6 weeks with OS or HU-671 completely rescues bone loss, whereas HU-681 has only a partial effect. The increased bone density was primarily due to enhanced trabecular thickness and number. Moreover, the most effective dose of HU-671 was 0.5 mg/kg/day, an order of magnitude lower than with OS. The reversal of bone loss resulted from increased bone formation and decreased bone resorption, as well as reversal of bone marrow adiposity. These results were further confirmed by determining the serum levels of osteocalcin and type 1 collagen C-terminal crosslinks, as well as demonstrating the enhanced antiadipogenic effect of HU-671. Taken together, these data suggest that methylation interferes with OS's metabolism, thus enhancing its effects by extending its availability to its target cells.


Assuntos
Adiposidade/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Ácidos Oleicos/química , Osteoporose/etiologia , Osteoporose/metabolismo , Serina/análogos & derivados , Serina/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Medula Óssea/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoporose/diagnóstico , Ovariectomia/efeitos adversos , Serina/química , Microtomografia por Raio-X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA